Restless Leg Syndrome


Restless leg syndrome (RLS), also known as Ekbom’s syndrome, is a discomfort, not pain, verbalized as pins and needles, a crawling sensation, or cramping mainly in the calves but sometimes noted in the thighs or arms. (1) Males and females are equally affected, and RLS occurs most commonly in the elderly. Iron deficiency, pregnancy, and renal failure are associated with RLS. Caffeine, stress, or fatigue may worsen the symptoms. (2) The sensation is generally bilateral and occurs only during rest and inactivity and is quickly relieved by walking or moving the legs. (3) When a patient attempts to resume sleep, the discomfort returns, causing insomnia. Clinical examination may reveal evidence of underlying systemic disease or mild peripheral neuropathy, but is more often normal. (4) Mild or intermittent symptoms usually require no treatment.


National Institute of Health, 2001.

    More than 80 percent of people with RLS also experience a more common condition known as periodic limb movement disorder (PLMD).

Signs and Symptoms

[span class=alert]The following list does not insure the presence of this health condition. Please see the text and your healthcare professional for more information.[/span]

Restless leg syndrome is often described as a discomfort rather than a pain, using terms such as pins and needles or a crawling sensation in the legs during recumbency. It is relieved upon standing or walking, but may return when the patient lies down again, often causing insomnia. Patients have an irresistible urge to move the legs around to relieve the discomfort. The symptoms may worsen during times of stress.


    Discomfort in legs when at rest or attempting sleep Sensation of creeping or crawling deep inside the calves or occasionally in the arms Irresistible urge to move legs Possible worsening of symptoms during times of stress

Treatment Options


Benzodiazepines are the first-line therapy, particularly for less severe cases and younger patients. Clonazepam, lorazepam, triazolam, and temazepam have been effective. Opiates, such as codeine and oxycodone, have been used; however, tolerance develops and abuse potential becomes a concern since the condition is chronic. Bromocriptine, clonidine, and carbamazepine have also been used. Tolerance may develop with any agent used; thus one approach is to alternate chemically unrelated agents weekly or bi-weekly. (5)

In the most severe cases, levodopa is used. The dose is 50mg given 30 minutes before bedtime. This dose may be titrated, and most patients achieve benefit from levodopa 200mg with carbidopa 50mg. (6) Rebound symptoms that may occur during the night and possibly during the day may be alleviated by using a sustained-release product, or dosing during the day.

Nutritional Supplementation


Biochemical and neurophysiological investigations were conducted in patients with magnesium deficiency. The EEG investigations revealed both neuromuscular excitability and conductibility. (7)

Another study reported that magnesium may be therapeutically effective in the treatment of individuals with insomnia related to restless leg syndrome. In this study, 10 patients (mean age 57 years old) were suffering from insomnia related to periodic limb movement during sleep (PLMS) or mild-to-moderate restless leg syndrome (RLS). Magnesium was administered orally at a dose of 12.4 mmol in the evening over a period of 4-6 weeks. Following magnesium treatment, limb movement associated with arousals decreased significantly, down from 17 to 7 events per hour of total sleep time. Periodic limb movements without arousal were also moderately reduced from 33 down to 21 incidents per hour of total sleep time. Sleep efficiency improved from 75% to 85%.

In the 7 patients who estimated that their sleep and/or symptoms of restless leg syndrome was improved after therapy, the effects of magnesium on periodic limb movement with and without arousal were even more pronounced. This study indicates that magnesium treatment may be a useful alternative therapy in patients with insomnia due to mild or moderate restless leg syndrome or periodic limb movements during sleep. (8)


Studies have reported that iron deficiency, with or without anemia, is an important contributor to the development of restless leg syndrome in elderly patients, and iron supplements can produce a significant reduction in symptoms. In an examination of 18 elderly patients with restless leg syndrome, compared to 18 matched controls, it was found that there were no differences in serum iron, vitamin B12, folic acid, and haemoglobin levels between the two groups. However, it was discovered that serum ferritin levels were inversely correlated with the severity of restless leg syndrome. Treatment with ferrous sulphate for 2 months resulted in a significant reduction in the score on the severity-of-symptoms rating scale. (9)

Folic Acid

One study in the scientific literature notes that restless leg syndrome is one of the neurological symptoms that can accompany folic acid deficiency. This study reports on six women between the ages of 31 to 70, who had folate deficiency and neuropsychiatric disorders. Some of the symptoms in three of the women with acquired folic acid deficiency included permanent muscular and intellectual fatigue, mild symptoms of restless legs, depressed ankle jerks, and a diminution of vibration sensation in the legs. All these symptoms resolved with folic acid therapy. The other three women were members of a family with restless legs syndrome, fatigability and diffuse muscular pain, in addition to a variety of other problems. Folic acid supplementation in the range of 5 to 10 mg daily resulted in dramatic improvement of symptoms. These authors state that unrecognized and treatable folate deficiency (with low serum folic acid values but normal erythrocyte folate values) may be the basis of a well defined syndrome of neurologic, psychiatric and gastroenterologic disorders, and the restless legs syndrome may represent the main clinical expression of acquired and familial (or inborn) folate deficiency in adults. (10)

Herbal Supplementation


Kava has been used for centuries by South Pacific natives. The root is used in the preparation of a recreational beverage known by a variety of local names (kava, yaqona, awa) and occupies a prominent position in the social, ceremonial, and daily life of Pacific island peoples as coffee or tea does in the Western cultures. In European phytomedicine, kava has long been used as a safe, effective treatment for mild anxiety states, nervous tension, muscular tension, and mild insomnia. (11) , (12) Studies have reported that kava preparations compare favorably to benzodiazepines in controlling symptoms of anxiety and minor depression, while increasing vigilance, sociability, memory, and reaction time. (13) , (14) Reports are conflicting as to whether kava’s anti-anxiety actions are GABA mediated. (15) , (16) Kavalactones appear to act on the limbic system, in particular the amygdala complex – the primitive part of the brain that is the center of the emotional being and basic survival functions. (17) It is thought that kava may promote relaxation, sleep, and rest by altering the way in which the limbic system modulates emotional processes. Tolerance does not seem to develop with kava use. (18) , (19)


Passionflower, or maypop, is a common roadside vine in many areas of the United States. Passionflower has been reported to have sedative, hypnotic, antispasmodic and anodyne properties. It has traditionally been used for neuralgia, generalized seizures, hysteria, nervous tachycardia, spasmodic asthma, and specifically for insomnia. (20) The bioactive constituents maltol and ethylmaltol have been shown to have CNS sedation, anticonvulsant activity (high doses), and a reduction in spontaneous motor activity (low doses) in laboratory animals. (21) Passionflower extracts have been reported to reduce locomotor activity, prolong sleeping time, raise the nociceptive threshold and produce an anxiolytic effect in laboratory animals. (22) In humans, passionflower has been reported effective when used in combination with other sedative and anti-anxiety herbs such as valerian, making it beneficial in conditions such as hyperthyroidism, where CNS stimulation occurs. (23) These effects may be due to synergism and also due to the potential binding of passionflower constituents to benzodiazepine receptors in vivo. (24) , (25)


Valerian has long been used as an agent to soothe the nervous system in response to stress. It has been reported that valerian helps improve sleep quality. (26) , (27) , (28) The usefulness of valerian is reported to be due to several principal components, including valepotriates, valeric acid and pungent oils which have a sedative effect on the central nervous system, as well as a relaxing effect on the smooth muscles of the GI tract. (29) , (30) It is felt that both valepotriates and valeric acid bind to receptor sites similar to the benzodiazepines. (31) Valerian’s constituents reportedly influence gamma-aminobutyric acid (GABA) activity through affinity for receptors in the brain. (32) Valerian does not seem to produce the morning drug hangover effect as seen with some benzodiazepines. (33)


  1. View Abstract: Ambrogetti A, Olson LG, Saunders NA. Disorders of movement and behavior during sleep. Med J Aust. 1991;155:336-340.
  2. Jermain DM. Sleep Disorders. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy, A Pathophysiologic Approach, 4th ed. Stamford, CT; 1999:1215.
  3. View Abstract: Krueger BR. Restless legs syndrome and periodic movements of sleep. Mayo Clin Proc. 1990;65:999-1006.
  4. Aminoff MJ. Parkinson’s Disease and other extrapyramidal disorders. In: Fauci AS, Braunwald E, Isselbacher KJ, et al, eds. Harrison’s Principles of Internal Medicine, 14th ed. New York: McGraw-Hill; 1998:2362.
  5. View Abstract: Krueger BR. Restless legs syndrome and periodic movements of sleep. Mayo Clin Proc. 1990;65:999-1006.
  6. View Abstract: Becker PM, Jamieson AO, Brown WD. Dopaminergic agents in restless legs syndrome and periodic limb movements of sleep: Response and complications of extended treatment in 49 cases. Sleep. 1993;16:713-716.
  7. View Abstract: Popoviciu L, et al. Clinical, EEG, electromyographic and polysomnographic studies in restless legs syndrome caused by magnesium deficiency. Rom J Neurol Psychiatry. Jan1993;31(1):55-61.
  8. View Abstract: Hornyak M, et al. Magnesium therapy for periodic leg movements-related insomnia and restless legs syndrome: an open pilot study. Sleep. Aug1998;21(5):501-5.
  9. View Abstract: O’Keeffe ST, Gavin K, Lavan JN. Iron status and restless legs syndrome in the elderly. Age Ageing. May1994;23(3):200-3.
  10. View Abstract: Botez MI, et al. Neurologic disorders responsive to folic acid therapy. Can Med Assoc J. Aug1976;115(3):217-23.
  11. View Abstract: Volz HP, et al. Kava-kava Extract WS 1490 Versus Placebo in Anxiety Disorders--A Randomized Placebo-controlled 25-week Outpatient Trial. Pharmacopsychiatry. Jan1997;30(1):1-5.
  12. View Abstract: Singh YN. Kava: An Overview. J Ethnopharmacol. Aug1992;37(1):13-45.
  13. View Abstract: MunteTF, et al. Effects of Oxazepam and an Extract of Kava Roots (Piper methysticum) on Event-related Potentials in a Word Recognition Task. Neuropsychobiology. 1993;27(1):46-53.
  14. Drug Therapy of Panic Disorders. Kava-specific Extract WS 1490 Compared to Benzodiazepines. Nervenarzt. Jan1994;65(1Supp):1-4.
  15. View Abstract: Jussofie A, et al. Kavapyrone Enriched Extract from Piper methysticum as Modulator of the GABA Binding Site in Different Regions of Rat Brain. Psychopharmacology. Berl. Dec1994;116(4):469-74.
  16. View Abstract: Davies LP, et al. Kava Pyrones and Resin: Studies on GABAA, GABAB and Benzodiazepine Binding Sites in Rodent Brain. Pharmacol Toxicol. Aug1992;71(2):120-26.
  17. View Abstract: Holm E, et al. The Action Profile of D,L-kavain. Cerebral Cites and Sleep-wakefulness-Rhythm in Animals. Arzneimittelforschung. Jul1991;41(7):673-83.
  18. View Abstract: Duffield PH, et al. Development of Tolerance to Kava in Mice. Clinical and Experimental Pharmacology & Physiology. 1991;18(8):571-78.
  19. View Abstract: Singh YN. Kava: An Overview. J Ethnopharmacol. Aug1992;37(1):13-45.
  20. Newall CA, et al. Herbal Medicines: A Guide for Health Care Professionals. London: The Pharmaceutical Press; 1996:206-207.
  21. Kimura R, et al. Central Depressant Effects of Maltol Analogs in Mice. Chem Pharm Bull. Tokyo. Sep1980;28(9):2570-2579.
  22. View Abstract: Soulimani R, et al. Behavioural Effects of Passiflora incarnata L. and Its Indole Alkaloid and Flavonoid Derivatives and Maltol in the Mouse. J Ethnopharmacol. Jun1997;57(1):11-20.
  23. View Abstract: Bourin M, et al. A Combination of Plant Extracts in the Treatment of Outpatients with Adjustment Disorder with Anxious Mood: Controlled Study Versus Placebo. Fundam Clin Pharmacol. 1997;11(2):127-132.
  24. View Abstract: Wolfman C, et al. Possible Anxiolytic Effects of Chrysin, A Central Benzodiazepine Receptor Ligand Isolated from Passiflora coerulea. Pharmacol Biochem Behav. Jan1994;47(1):1-4.
  25. Spreoni E, et al. Neuropharmacological Activity of Extracts from Passiflora incarnata. Planta Med. Dec1988;54(6):488-91.
  26. View Abstract: Lindahl O, Lindwall L. Double Blind Study of Valerian Preparations. Pharmacol. Biochem. Behav. 1989;32(4):1065-66.
  27. View Abstract: Leathwood PD, et al. Aqueous Extract of Valerian Root (Valeriana officinalis L.) Improves Sleep Quality in Man. Pharmacol Biochem Behav. 1982;17:65-71.
  28. View Abstract: Balderer G, et al. Effect of Valerian on Human Sleep. Psvchopharmacology. 1985;87:406-09.
  29. Wagner H, et al. On the Spasmolytic Activity of Valeriana Extracts. Planta Med. 1979;37(1):84-86.
  30. Hendriks H, et al. Pharmacological Screening of Valerenal and Some Other Components of Essential Oil of Valeriana officinalis. Planta Medica. 1985;51:28-31.
  31. View Abstract: Houghton PJ. The Biological Activity of Valerian and Related Plants. J Ethnopharmacol. 1988;22(2):121-42.
  32. View Abstract: Santos MS, et al. Synaptosomal GABA Release as Influenced by Valerian Root Extract--Involvement of the GABA Carrier. Arch Int Pharmacodyn Ther. 1994;327(2):220-31.
  33. View Abstract: Leathwood PD, et al. Aqueous Extract of Valerian Root (Valeriana officinalis L.) Improves Sleep Quality in Man. Pharmacol Biochem Behav. 1982;17:65-71.